Abstract

2229

Selenium is a proposed chemopreventive agent and is a component of the NCI-sponsored SELECT prostate cancer chemoprevention trial. Yet the actual mechanism by which Selenium may provide a protective basis has yet to be elucidated. Here we describe a series of genomic profiling studies carried out using rat and human prostate cancer cell lines treated with Selenium. Associated genomic profiling studies were carried out using rat and human spotted cDNA arrays and cross-species bioinformatics analysis performed along with gene based data mining and metabolic/biologic pathway mapping. These studies identified a series of genes and pathways that were dysregulated in the presence of Selenium. These included pathways involved in stress response (including modulation of glutathione-S-transferases), retinoid metabolism, and cell cycle regulation. Specific genes of interest included the identification of IGFBP3, RXR-alpha, and Bcl-2, as genes induced by Selenium treatment. Tissue microarray studies reveal both IGFBP3 and RXR-alpha to be significantly associated with prostate cancer formation. These genes and pathways may provide a biomarker for evaluating Selenium chemoprevention, or could be used in the development of combination chemoprevention protocols.